Streptococcus pneumoniae is the most frequent cause of bacterial pneumonia in children of developing countries and accounts for up to 76% of cases in adults (Pennington, 1986, Am. Fam. Physician 33:153; Johnston, 1991, Revs. Infect. Dis. 13 (Suppl. 6):S509; Musher, 1992, Clin. Infect. Dis. 14:801). Pneumococci generally enter the host via the nasopharynx where they attach to epithelial cells and in some instances persist for several months (Anderson et al., 1981, Infect. Immun. 32:311). In experimental models, progression to pneumonia results from spread of the pneumococci by aerosolization and conveyance from the nasopharynx down into the lower respiratory tract.
The early pneumonic lesion is characterized by fluid filled alveoli containing pneumococci, which are frequently seen to line the alveolar walls, a distribution suggestive of a specific interaction promoting retention in the alveolar space (Wood, 1941, J. Exp. Med. 73:222). Pneumococci readily gain access to the blood circulation from the alveolar space, suggesting an aggressive capability to cross the vascular endothelial cells of the alveolar capillaries (Rake, 1936, J. Exp. Med. 63:191).
Bacterial adherence to eukaryotic cells commonly involves specific bacterial proteins (adhesions) which recognize host cell glycoconjugates. Adherence of pneumococci to human oral epithelium is inhibited in the presence of the disaccharide N-acetyl-glucosamine-.beta.1-3-galactose (GlcNAc.beta.1-3Gal) suggesting that this carbohydrate can serve as a receptor, perhaps relevant to nasopharyngeal carriage (Anderson et al., 1983, J. Exp. Med. 158:559). It remains unknown precisely which cell type supports pneumococcal adherence in the alveolar space. Pneumococci have been reported to bind to purified glycoconjugates containing terminal or internal GalNAc.beta.1-4Gal, a structure prevalent in pulmonary secretions and lung tissue (Krivan et al., 1988, Proc. Natl. Acad. Sci. USA 85:6157). This structure differs significantly in stereochemistry from that proposed for the nasopharyngeal receptor.
The identity of pneumococcal adhesions capable of mediating attachment to the nasopharynx and lung is unknown. Consistent with the ability to readily cause experimental bacteremia, pneumococcal adherence to vascular endothelial cells has been shown to be dose-dependent, rapid and independent of capsular type (Geelen et al., 1993, Infec. Immun. 61:1538). Both cell-wall components and protein components contribute roughly equally to this association, but specific pneumococcal ligands remain to be identified (Tuomanen et al., 1985, J. Infect. Dis. 151:859).
The citation of references herein shall not be construed as an admission that such is prior art to the present invention.